Overexpression of p53 is associated with growth pattern and prognosis in advanced gastric cancer.

BACKGROUND/AIMS: The growth pattern of advanced gastric carcinoma, based on volumetric analysis, is closely associated with the biological characteristics of tumors, including DNA ploidy, and is an important prognostic factor. Abnormality of the p53 tumor suppressor gene plays an important role in alteration of cells and possibly leads to cancer development.

MATERIALS AND METHODS

Expression of tumor suppressor gene p53 was investigated immunohistochemically in the primary lesion of 196 patients with advanced gastric cancers, and the relationship of p53 immunopositivity with the growth pattern and prognosis was analyzed.

RESULTS

Positive p53 staining was found in 94 (48%) of the 196 primary carcinomas. Vessel invasions were more frequent and lymph node metastasis was more extensive in p53-positive tumors (p < 0.05), whereas p53 immunopositivity was not associated with depth of cancer invasion nor with the stage of cancer. In the column and mountain type tumors, characterized by vertical or penetrative growth, positive p53 staining was found in 53.8% and 52.9%, respectively. In the funnel type tumor, characterized by superficially spreading growth, positive p53 staining was found in significantly lower incidence (28.9%, p < 0.05). The 5-year survival rates were 44.2% and 25.4% for patients with p53 negative and positive gastric carcinomas, respectively (p < 0.01). Multivariate analysis showed that p53 overexpression was an independent prognostic factor of patients with advanced gastric cancer.

CONCLUSIONS

These findings suggest that p53 gene alteration is associated with less favorable prognosis of advanced gastric cancer, possibly by providing tumors with a potential of vertical growth into the gastric wall.